title: Design of an acid-activated antimicrobial peptide for tumor therapy.
abstract: Antimicrobial peptides have received increasing attention as potential antitumor drugs due to their new mode of action. However, the systemic toxicity at high concentration always hampers their successful utilization for tumor therapy. Here, we designed a new type of acid-activated antimicrobial peptide AMitP by conjugating antimicrobial peptide MitP to its anionic binding partner MitPE via a disulfide linker. Compared with MitP, AMitP displayed significant antitumor activity at acidic pH and low cytotoxicity at normal pH. The results of MD simulations demonstrate that the changes of structure and membrane binding tendency of AMitP at different pH values played an important role in its pH-dependent antitumor activity. In addition, AMitP showed significant enzymatic stability compared with MitP, suggesting a potential for in vivo application. In short, our work opens a new avenue to develop antimicrobial peptides as potential antitumor drugs with high selectivity.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University , Lanzhou 730000, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Kai
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.forename: Ranran
authors.initials: R
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Guolin
authors.initials: G
authors.lastname: Li
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Yang
authors.forename: Jingman
authors.initials: J
authors.lastname: Ni
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004795:Enzyme Stability / Q000187:drug effects; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D011419:Propidium / Q000737:chemistry; D011485:Protein Binding; D014862:Wasp Venoms
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides; D014862:Wasp Venoms; C529760:mitoparan; D011419:Propidium